Symptoms and General Pathology

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Stevens-Johnson Syndrome

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Conjunctival Diseases

Bullous Pemphigoid

Mucous Membrane Pemphigoid

Stevens-Johnson Syndrome/toxic Epidermal Necrolysis

Anti-Inflammatory Agents

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All Drugs and Chemicals

Infliximab

Tumor Necrosis Factor Inhibitors

topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months

topical infliximab administered QID for 3 months followed by BID for 9 months

topical infliximab

James Chodosh, MD, MPH

Claes H Dohlman, MD, PhD

Mona Harissi-Dagher, MD

The Boston Keratoprosthesis type I (KPro) is a prosthetic cornea used to treat several causes of corneal blindness. Some categories of patients, including those with auto-immune diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome and mucous membrane pemphigoid, have a higher risk of failure for the KPro. Because of chronic inflammation, the cornea supporting the KPro may melt, leading to a higher risk of infection, loss of the KPro and loss of the eye.

Infliximab is an antibody against tumor necrosis factor alpha and is used intravenously to control inflammation in several diseases. It has been used in some cases of corneal melting with significant success.

This study's hypothesis is that infliximab can be successfully used as an eye drop (instead of the usual administration through veins) and that its regular use may prevent melt in eyes with a Boston Keratoprosthesis type I and underlying auto-immune disease.

This is an unmasked, prospective, multicenter clinical trial of four patients that are candidates for a Boston Keratoprosthesis or have had prior KPro surgery and have a diagnosis of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis syndrome (TENS) or mucous membrane pemphigoid (MMP). Only one eye per patient will be considered for inclusion.

This is a phase I/II study to evaluate the safety and tolerance of topical infliximab 10 mg/mL eye drops. Research subjects will be required to administer infliximab eye drops four times per day for three months followed by twice daily administration for nine months. The subjects will be monitored while on the study medication as well as for one year following discontinuation of the drug. The total study duration for each patient will be two years.

Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Percentage of patients finishing 12 months of topical infliximab use

rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)

Ocular surface symptoms as assessed by ocular surface disease index score

Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)

Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1

Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab

Massachusetts Eye and Ear Infirmary

Fonds de recherche en ophtalmologie de l'Université de Montréal

Associate Director of the Cornea and Refractive Surgery Service, Director of Boston Keratoprosthesis Clinical Programs

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

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Rectal Neoplasms

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Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

Fluorouracil

Cisplatin

Chemotherapy (C/T) is applied in the morning. After 2-4 hrs, radiotherapy (RT) is delivered (according to the clinical practice)

Radiotherapy (RT) is delivered in the morning. After 2-4 hrs, chemotherapy (C/T) is applied (according to the clinical practice).

Radiation therapy (RT) is used as an effective local treatment modality to inhibit cell proliferation, induce cell death and suppress tumor growth. To improve the treatment outcome, in terms of both locoregional control and survival, the concurrent use of chemotherapy during radiation therapy (CCRT) is now the standard treatment for various malignancies, especially locally advanced cancers. Among the drugs used to enhance RT effect, 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents of CCRT.

In the past, RT was solely used as a local treatment and its effect was estimated by local effect model. However, growing evidence shows that irradiation has direct DNA damage-dependent effects as well as sending signals to neighboring cells. Recently, we reported that abdominal irradiation could significantly modulate the systemic pharmacokinetics of 5-FU at 0.5 Gy, off-target area in clinical practice, and at 2 Gy, the daily treatment dose for target treatment in an experimental rat model. Additionally, the results from a clinical investigation showed that colorectal cancer patients with lower AUC of 5-FU during adjuvant chemotherapy had lower disease-free survival. Taken together, these lines of evidence support the importance and necessity to search for the mediators responsible for the unexpected effect of local RT on systemic pharmacokinetics of chemotherapeutic agents, such as 5-FU.

In the present study, the investigators investigated whether the phenomena and mechanism of RT-PK is a fact for different anticancer drugs in human.

Irradiation Modulates the Pharmacokinetics of Anticancer Drugs

Far Eastern Memorial Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Topical Infliximab in Autoimmune Eyes With Keratoprosthesis	NCT02126020	Stevens-Johnson... Toxic Epidermal... Mucous Membrane...	topical inflixi...	18 Years - 80 Years	Massachusetts Eye and Ear Infirmary
Irradiation Modulates the Pharmacokinetics of Anticancer Drugs	NCT01755585	Rectal Cancer Cervical Cancer		18 Years - 80 Years	Far Eastern Memorial Hospital

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